rs75543046

Variant names:

• chr9-677089-G-A
• rs75543046
• NM_015158.5:c.37+80G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015158.5(KANK1):​c.37+80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 1,281,958 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (81 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (59 hom.)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.718
• Publications: 1 publications found

Genes affected

KANK1 (HGNC:19309): (KN motif and ankyrin repeat domains 1) The protein encoded by this gene belongs to the Kank family of proteins, which contain multiple ankyrin repeat domains. This family member functions in cytoskeleton formation by regulating actin polymerization. This gene is a candidate tumor suppressor for renal cell carcinoma. Mutations in this gene cause cerebral palsy spastic quadriplegic type 2, a central nervous system development disorder. A t(5;9) translocation results in fusion of the platelet-derived growth factor receptor beta gene (PDGFRB) on chromosome 5 with this gene in a myeloproliferative neoplasm featuring severe thrombocythemia. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 20. [provided by RefSeq, Dec 2014]

KANK1 Gene-Disease associations (from GenCC):

• spastic quadriplegic cerebral palsy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• cerebral palsy, spastic quadriplegic, 2

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

KANK1-AS1 (HGNC:58139):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-677089-G-A is Benign according to our data. Variant chr9-677089-G-A is described in ClinVar as Benign. ClinVar VariationId is 1242096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0552 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015158.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANK1	NM_015158.5	MANE Select	c.37+80G>A		intron	N/A	NP_055973.2	Q14678-1
	KANK1	NM_001256876.3		c.37+80G>A		intron	N/A	NP_001243805.1	Q14678-1
	KANK1	NM_001256877.3		c.37+80G>A		intron	N/A	NP_001243806.1	Q14678-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANK1	ENST00000382297.7	TSL:1 MANE Select	c.37+80G>A		intron	N/A	ENSP00000371734.2	Q14678-1
	KANK1	ENST00000382303.5	TSL:1	c.37+80G>A		intron	N/A	ENSP00000371740.1	Q14678-1
	KANK1	ENST00000382289.7	TSL:1	c.37+80G>A		intron	N/A	ENSP00000371726.3	Q5W0W3

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2520 AN: 152052 Hom.: 81 Cov.: 33

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00187 AC: 2108 AN: 1129788 Hom.: 59 AF XY: 0.00159 AC XY: 904 AN XY: 570014

African (AFR) AF: 0.0615 AC: 1588 AN: 25832

American (AMR) AF: 0.00312 AC: 118 AN: 37790

Ashkenazi Jewish (ASJ) AF: 0.0000866 AC: 2 AN: 23082

East Asian (EAS) AF: 0.00 AC: 0 AN: 36760

South Asian (SAS) AF: 0.000191 AC: 14 AN: 73448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52254

Middle Eastern (MID) AF: 0.00280 AC: 14 AN: 5008

European-Non Finnish (NFE) AF: 0.000214 AC: 177 AN: 826760

Other (OTH) AF: 0.00399 AC: 195 AN: 48854

GnomAD4 genome AF: 0.0166 AC: 2521 AN: 152170 Hom.: 81 Cov.: 33 AF XY: 0.0159 AC XY: 1183 AN XY: 74386

African (AFR) AF: 0.0571 AC: 2368 AN: 41480

American (AMR) AF: 0.00700 AC: 107 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68022

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.0123 Hom.: 8

Bravo AF: 0.0194

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.0
DANN	Benign	0.67
PhyloP100		0.72
PromoterAI		-0.0088	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs75543046; hg19: chr9-677089;